Genetic polymorphisms of epidermal growth factor in relation to risk of hepatocellular carcinoma: Two case-control studies

Jian Min Yuan, Yunhua Fan, Simona Ognjanovic, Renwei Wang, David Van Den Berg, Sugantha Govindarajan, Mimi C. Yu

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14 Scopus citations


Background: Earlier, we reported a highly statistically significant association between T-helper 1 (Th1) and Th2 cytokine genotypes and hepatocellular carcinoma (HCC) risk among natives of southern Guangxi, China, a hyperendemic region for HCC. Epidermal growth factor (EGF) plays a critical role in malignant transformation of hepatocytes and tumor progression. A polymorphism in the EGF gene (61A > G) results in elevation of EGF in liver tissues and blood. Epidemiological data are sparse on the possible association between EGF genetic polymorphism and HCC risk. Methods: The EGF 61A > G polymorphism, multiple Th1 and Th2 genotypes, and environmental risk factors for HCC were determined on 117 HCC cases and 225 healthy control subjects among non-Asians of Los Angeles County, California, a low-risk population for HCC, and 250 HCC cases and 245 controls of southern Guangxi, China. Results: Following adjustment for all known or suspected HCC risk factors, non-Asians in Los Angeles who possessed at least one copy of the high activity 61*G allele of the EGF gene showed a statistically non-significant, 78% increased risk of HCC compared with those possessing the EGF A/A genotype. This EGF-HCC risk association significantly strengthened among heavy users of alcohol [odds ratio (OR) = 3.44, 95% confidence interval (CI) = 0.93-12.76, P = 0.065)], and among individuals carrying the high-risk Th1/Th2 genotypes for HCC (OR = 3.34, 95% CI = 1.24-9.03, P = 0.017). No association between EGF genotype and HCC risk was observed among Chinese in southern Guangxi, China. Conclusion: Genetic polymorphism in the EGF gene resulting in elevated level of EGF, may contribute to HCC risk among low-risk non-Asians in Los Angeles.

Original languageEnglish (US)
Article number32
JournalBMC Gastroenterology
Issue number1
StatePublished - Feb 18 2013

Bibliographical note

Funding Information:
We thank Dr. Zhen-Quan Zhang at the Cancer Institute of Guangxi, China, for implementing the case–control study of hepatocellular carcinoma in Guangxi, China. The study was supported in part by grants R01 CA80205 (to Yu), and R01 CA144034 (to Yuan) from the United States National Institutes of Health. The funding agency has no role in design of the study; in the collection, analysis, and interpretation of data; in the writing of the manuscript; and in the decision to submit the manuscript for publication.


  • Cytokines
  • Epidermal growth factor
  • Hepatocellular carcinoma
  • T-helper


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